The proposed research will be the first to test the theory of syndemics among a vulnerable population. The syndemics concept, in contrast to the epidemics concept, provides an innovative theoretical and practical approach that combines concepts of ?synergy? with ?epidemic? to investigate how social, political, and ecological factors promote disease clustering at the population-level and impact disease pathologies at the individual-level. The notion of syndemic incorporates three core concepts: 1) two or more diseases cluster together within a population, 2) these diseases interact, often biologically, and 3) large-scale social forces precipitate them. Syndemic clusters with Type 2 diabetes (T2DM) among black South Africans exemplify the syndemics concept, and in-depth investigation of this phenomenon will provide important policy and clinical perspectives. T2DM is escalating among low-income populations in low- and middle-income countries, with T2DM affecting people younger than 60 years of age and often going undiagnosed. Co-occurring conditions, including depression, are common and afflict women disproportionately residing in low-resource settings. The proposed research will recruit 5,000 individuals enrolled in an established surveillance study to create a platform to syndemic clusters. The first aim will test syndemic theory by evaluating the social and economic factors that produce syndemic clusters of T2DM, with hypertension (HTN), depression, HIV, and tuberculosis (TB), from that surveillance platform. We hypothesize that social and economic determinants of co-occurring conditions will differ from those determinants that foster singular diseases apart from syndemic clusters. The second aim will employ mixed methods to investigate the social and medical experiences and health care behaviors among 150 people with T2DM and co-occurring HTN, HIV, TB, or depression to examine what social and biological experiences characterize these syndemic clusters. We hypothesize that unique social, economic, psychological, and personal experiences will afflict people experiencing one syndemic cluster compared to another. These data will be imperative during the planning stages of the new primary care system currently underway in South Africa, and we anticipate that insights into integrated primary care will be timely, relevant, and informative. The public health impact of this research is to 1) demonstrate that using a syndemics framework is more effective than a singular disease framework to evaluate complicated disease events, 2) inform social policy, such as the new sugar sweetened beverage tax in South Africa, and 3) provide targeted information for integrated primary care that can inform the restructuring of the South African health system underway. The design of integrated clinical interventions as well as the preliminary research to support further research on syndemics will have broader applicability to clinical care in the U.S. and other syndemic conditions.